The onset of rare earth metallosis begins with renal gadolinium-rich nanoparticles from magnetic resonance imaging contrast agent exposure (2023).

Article link: https://www.nature.com/articles/s41598-023-28666-1

Authors and Affiliations:

Joshua DeAguero 1 2 3, Tamara Howard 4, Donna Kusewitt 4, Adrian Brearley 5, Abdul-Mehdi Ali 5, James H Degnan 6, Stephen Jett 7, John Watt 8, G Patricia Escobar 9 4 10, Karol Dokladny 9 4 10, Brent Wagner 11 12 13

• 1Kidney Institute of New Mexico, University of New Mexico Health Science Center, Albuquerque, NM, USA. joshdeaguero@salud.unm.edu.

• 2University of New Mexico Health Science Center, Albuquerque, NM, USA. joshdeaguero@salud.unm.edu.

• 3New Mexico Veterans Administration Health Care System, Albuquerque, NM, USA. joshdeaguero@salud.unm.edu.

• 4University of New Mexico Health Science Center, Albuquerque, NM, USA.

• 5Department of Earth and Planetary Sciences, University of New Mexico, Albuquerque, NM, USA.

• 6Department of Mathematics and Statistics, University of New Mexico, Albuquerque, NM, USA.

• 7Chan Zuckerberg Initiative, Redwood City, CA, USA.

• 8Center for Integrated Nanotechnologies, Los Alamos National Laboratory, Los Alamos, NM, 87545, USA.

• 9Kidney Institute of New Mexico, University of New Mexico Health Science Center, Albuquerque, NM, USA.

• 10New Mexico Veterans Administration Health Care System, Albuquerque, NM, USA.

• 11Kidney Institute of New Mexico, University of New Mexico Health Science Center, Albuquerque, NM, USA. BrWagner@salud.unm.edu.

• 12University of New Mexico Health Science Center, Albuquerque, NM, USA. BrWagner@salud.unm.edu.

• 13New Mexico Veterans Administration Health Care System, Albuquerque, NM, USA. BrWagner@salud.unm.edu.

Summary: “MRI contrast agent treatment resulted in unilamellar vesicles and mitochondriopathy in renal epithelium. Electron-dense intracellular precipitates and the outer rim of lipid droplets were rich in gadolinium and phosphorus. We conclude that MRI contrast agents are not physiologically inert. The long-term safety of these synthetic metal-ligand complexes, especially with repeated use, should be studied further”.

“Concomitant with the Warburg effect in the kidney, systemic gadolinium-based contrast agent treatment induces dyslipidemia and insulin resistance. The impact of gadolinium-based contrast agent treatment in the liver was examined. Gadolinium increased intracellular triglycerides as assessed by oil red O staining. Electron microscopy revealed that gadolinium treatment increased unilamellar vesicles and reduced mitochondrial volume. Metabolomic analysis of the livers demonstrated alterations in metabolites associated with amino acid metabolism, glycogenesis, and glycolysis. These findings support the hypothesis that gadolinium-based contrast agents are not biologically inert.”

“Principal component analysis supported the correlations of phosphorus and gadolinium in precipitates (Fig. S12). These data show that gadolinium de-chelates from MRI contrast agent formulations and precipitates intracellularly. This phenomenon is concomitant with lipid vacuolization, mitochondrial damage, and subacute tubular damage”.

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Commentary: De-chelated! Gadolinium de-chelates from proprietary chelator, forming precipitates intracellularly, causing renal mitochondrial damage and liver metabolomic alterations.